Members of the group III atypical mycobacteria are causative agents of pulmonary disease in man. Pathogenicity of mycobacteria appears to be correlated with a slow rate of growth; in general, strains of mycobacteria with rapid rates of growth are primarily saprophytes. The purpose of this investigation is to delineate the metabolic and the genetic factors that contribute to the pathogenicity of a group III organism, Mycobacterium avium, which has a slow rate of growth. M. avium produces two closely related variants that are distinguishable by colony morphology, pathogenicity, drug resistance and nutritional requirements. It also exhibits a life cycle in which short rods elongate to form filaments and these fragment to produce coccobacilli. These unique characteristics will be used in assessing the effect of cell envelope synthesis and ultimate composition on cell morphology and pathogenicity. The biological function of the cell envelopes of the two variants at the various phases of growth and fragmentation will be measured by determining their permeability to exogenous materials and their resistance to host cell digestion. The long range goal is to discover the genetic basis for the origin of the two variants in order to characterize pathogenicity of M. avium at the molecular level.